Objectives/Hypothesis Define surgical outcomes of specific donor sites for free tissue transfer in head and neck reconstruction. Study Design Retrospective cohort review at an academic tertiary care center. Methods A review was made of free tissue transfer procedures performed at a university-based tertiary care facility from October 2004 to April 2011. A total of 1,051 patients underwent six types of free flaps: fasciocutaneous radial forearm (53%), osteocutaneous radial forearm (16%), rectus abdominis (11%), fibula (10%), anterior lateral thigh (7%), and latissimus dorsi (2%). Demographic data were collected, and outcomes measured were: length of hospital stay, flap viability, and major complications (infection, fistula, and hematoma). Results Of the 1,051 flaps performed, the most common operative site was oral cavity (40%, n = 414) followed by hypopharynx/larynx (22%, n = 234), cutaneous (20%, n = 206), oropharynx (9%, n = 98), midface (7%, n = 76), and skull base (2%, n = 23). The median hospital stay was 7.9 days (range, 1-76), and the overall failure rate was 2.8%. Cutaneous defects required the shortest length of hospitalization (5.8 days, P <.0001), a low free flap failure rate (1.5%, n = 3), and limited major complications (6%, n = 12). Conversely, oropharynx defects were associated with the longest hospitalization (8.9 days). Midface defects had a high incidence of complications (15%, n = 11, P =.10). Defects above the angle of the mandible had higher overall complications when compared to below. Similarly, reconstruction for primary or recurrent cancer had a total failure rate of 2.5%, whereas secondary reconstruction and radionecrosis had a failure rate of 4.0% (P =.29). Additionally, there was no statistical difference between outcomes based on donor site. Conclusions This review demonstrates that certain subsets of patients are at higher risk for complications after free tissue transfer. Patients undergoing free flap reconstruction for cutaneous defects have substantially shorter hospital stays and are at lower risk of flap complications, whereas reconstruction for radionecrosis and secondary reconstruction tend to have higher overall flap failure rates. Level of Evidence 2c. Laryngoscope, 2013 Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.